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Search for New Anti-Cancer Seeds Targeting for cell Differentiation and cell Cycle

Research Project

Project/Area Number 13470470
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionOsaka University

Principal Investigator

KOBAYASI Motomasa  Professor Faculty of Pharmaceutical Sciences, Osaka University,, 薬学研究科, 教授 (40116033)

Co-Investigator(Kenkyū-buntansha) AOKI Shunji  Assistant Professor Faculty of Pharmaceutical Sciences, Osaka University,, 薬学研究科, 講師 (60252699)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2001: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsIndonesia / Marine sponge / Cell differentiation / Anti-tumor / Biological active / cell cycle
Research Abstract

In search of new anti-cancer substance from marine organisms, we have constructed the following four bioassay systems and screened the extracts of the marine sponges, which we have collected in the fields.
(1) Search for differentiation inducer against K562 cells to erythrocyte or macrophage
(2) search for inducer of neuronal differentiation against neuroblastoma Neuro 2A cells
(3) search for inducer against ras-transformed cells to normal cell
(4) search for selective inhibitor of cell cycle. we have screened about 400 extracts of marine sponges, and the active extracts were further subjected to fractionation and isolation on the guidance of the above bioassay systems. The results summarize as follows.
1. As for the neuritogenic long-chain polyketide, lembehyne A, we achieved the first total synthesis. Further analong synthesis of lembehyne A and structure-activity relationship study clarified that 3R-hydroxy-1-yen structure and proper length of long-chain play a important role for neurito … More genic activity of lembehyne A. Lembehyne A induced increase of cycline-dependent kinase P21 and arrested cell cycle of Neuro 2A cell at the G1 phase and also esterase. In order to elucidate target protein of lembehyne A, we designed and synthesized a radioactive photoaffinity probe of lembehyne A.
2. An alkaloid, hymenialdisine, isolated from Indonesian marine sponge induced differentiation of K562 cells to macrophage. Hymenialdisine induced morphological changes, G2/M arrest of cell cycle, reduction of NBT, and increase of acetylcholine esterase against K562 cells. Hymenialdisine also inhibited CDK1/cvcB complex, which might be one of target protein.
3. Pyridoacridine alkaloids isolated from Indonesian marine sponge induced neuritogenesis against Neuro 2A cell and increase of acetylcholine esterase lebel and arresed cell cycle at the G2/M phase.
4. A novel anthracycline, komodoquinone A, isolated from the solid-state fermentation of streptomyces sp. Induced differentiation and G1 arrest against Neuro 2A cells. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(37 results)

All Other

All Publications

  • [Publications] S.Aoki: "Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell"Biochem.Biophys.Res.Commun.. 289. 558-563 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Differentiation in chronic myelogenous leukemia cell K562 by spongean sesterterpene"Biochem.Biophys.Res.Commun.. 282. 426-431 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Reversing effect of agosterol A, a spongean sterol acetate, on multidrug resistance in human carcinoma cells"Jpn.J.Cancer Res.. 92. 886-895 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Murakami: "Total synthesis of lembehyne A, a neurogenic spongean polyacetylene"Tetrahedron Lett.. 42. 1941-1943 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp."Tetrahedron. 56. 9945-9948 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Brianthein A, a novel briarane-type diterpene reversing multidrug resistance in human carcinoma cell line, from the gorgonian"Tetrahedron. 57. 8951-8957 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Kobayashi: "Search for biologically active substances from marine sponges"Drugs from the Sea, N.Fusetani (ed.)(Basel, Karger). 46-58 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Structure-activity relationship of neuritogenic spongean acetylene alcohols lembehynes"Tetrahedron. 58. 5417-5422 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Lembehsterols A and B, novel sulfated sterols inhibiting thymidine phosphorylase, from the marine sponge Petrosia strongylata"Chem.Pharm.Bull.. 50-6. 827-830 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "pyridoacridine alkaloids inducing neuronal differentiation in a neuroblastoma cell line, from marine sponge Biemna fortis"Bioorg. & Med.Chem.. 11. 1969-1973 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Murakami: "New readily accessible peroxides with high anti-malarial potency"Bioorg. & Med.Chem.Lett.. 12. 69-72 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Murakami: "New Rev-transport inhibitor with anti-HIV activity from Valerianae Radix"Bioorg. & Med.Chem.Lett.. 12. 2807-2810 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Ozaki: "Inhibitory mechanism of xestospongin-C on contraction and ion channels in the intestinal smooth muscle"British J.Pharmacol.. 137. 2807-2810 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Wei H, Matsui H, Rachmat R, Kobayashi M: "Pyridoacridine alkaloids inducing neuronal differentiation in a neuroblastoma cell line, from marine sponge Biemna fortis"BIOORGANIC & MEDICINAL CHEMISTRY. 11(3). 1969-1973 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Matsui K, Wei H, Murakami N, Kobayashi M: "Structure-activity relationship of neuritogenic spongean acetylene alcohols, lembehynes"TETRAHEDRON. 58(27). 5417-5422 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Naka Y, Itoh T, Furukawa T, Rachmat R, Akiyama S, Kobayashi M: "Lembehsterols A and B, novel sulfated sterols inhibiting thymidine phosphorylase, from the marine sponge Petrosia strongylata"CHEMICAL & PHARMACEUTICAL BULLETIN. 50(6). 827-830 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami N, Ye Y, Kawanishi M, Aoki S, Kudo N, Yoshida M, Nakayama EE, Shioda T, Kobayashi M: "New Rev-trsnsport inhibitor with anti-HTV activity from Valerianae Radix"BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 12(20). 2807-2810 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ozaki H, Hori M, Kim YS, Kwon SC, Ahn DS, Nakazawa H, Kobayashi M, Karaki H: "Inhibitory mechanism of xestosponign-C on contraction and ion channels in the intestinal smooth muscle"BRITISH JOURNAL OF PHARMACOLOGY. 137(8). 1207-1211 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Matsui K, Takata T, Hong W, Kobayashi M: "Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 289(2). 558-563 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Okano M, Matsui K, Itoh T, Satari R, Akiyama S, Kobayashi M: "Brianthein A, a novel briarane-type diterpene reversing multidrug resistance in human carcinoma cell line, from the gorgonian Briareum excavatum"TETRAHEDRON. 57(43). 8951-8957 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Ye Y, Higuchi K, Takashima A, Tnaka Y, Kitagawa I, Kobayashi M: "Novel neuronal nitric oxide synthase (nNOS) selective inhibitor, aplysinopsin-type indole aikakoid, from marine sponge Hyrtios erecta"CHEMICAL & PHARMACEUTICAL BULLETIN. 49(10). 1372-1374 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Chen ZS, Higasiyama K, Setiawan A, Akiyama S, Kobayashi M: "Reversing effect of agosterol A, a spongean sterol acetate, on multidrug resistance in human carcinoman cells"JAPANESE JOURNAL OF CANCER RESEARCH. 92(8). 886-895 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki S, Higuchi K, Isozumi N, Matsui K, Miyamoto Y, Itoh N, Tanaka K, Kobayashi M: "Differentiation in chronic myelongenous leukemia cell K562 by spongean sesterterpene"BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 282(2). 426-431 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami N, Mostaqul HM, Tamura S, Itagaki S, Horii T, Kobayashi M: "New anti-malarial flavonol glycoside from Hydrangeae Dulcis Folium"BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 11(18). 2445-2447 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami N, Nakajima T, Kobayashi M: "Total synthesis of lembehyne A, a neurtogenic spongeam polyacetylene"TETRAHEDRON LETTERS. 42(10). 1941-1943 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aoki: "Structure-activity relationship of neuritogenic spongean acetylene alcohols, lembehynes"Tetrahedron. 58. 5417-5422 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Aoki: "Lembehsterols A and B, novel sulfated sterols inhibiting thymidine phosphorylase, from the marine sponge Petrosia strongylata"Chem. Pharm. Bull.. 50. 827-830 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Aoki: "Pyridoacridine alkaloids inducing neuronal differentiation in a neuroblastoma cell line, from marine sponge Biemna fortis"Bioorg. & Med. Chem.. 11(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Murakami: "New readily accessible peroxides with high anti-malarial potency"Bioorg. & Med. Chem. Lett.. 12. 69-72 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Aoki: "Brianthein A, a novel briarane-type diterpene reversing multidrug resistance in human carcinoma cell line, from the gorgonian"Tetrahedron. 57. 8951-8957 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Murakami: "Total synthesis of lembehyne A, a neurogenic spongean polyacetylene"Tetrahedron Lett.. 42. 1941-1943 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Aoki: "Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell"Biochem.Biophys.Res.Commun.. 289. 558-563 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Aoki: "Differentiation in chronic myelogenous leukemia cell K562 by spongean sesterterpene"Biochem.Biophys.Res.Commun.. 282. 426-431 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Aoki: "Reversing effect of agosterol A, a spongean sterol acetate, on multidrug resistance in human carcinoma cells"Jpn.J.Cancer Res.. 92. 886-895 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Murakami: "Total synthesis of lembehyne A, a neurogenic spongean polyacetylene"Tetrahedron Lett.. 42. 1941-1943 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Aoki: "Lembehyne A, a novel neuritogenic polyacetylene, from a marine sponge of Haliclona sp."Tetrahedron. 56. 9945-9948 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Kobayashi: "N.Fusetani(ed.) Drugs from the sea, Basel, Karger"Search for biologically active substances from marine sponges. 46-58 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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